Abstract: The disclosure features methods for treating hypophosphatasia (HPP) in a patient (e.g., a child having HPP) exhibiting physical impairments, disability in activities of daily living (ADL), pain, and/or delayed motor development by administering a soluble alkaline phosphatase (sALP) to the patient.

Abstract: This invention provides, inter alia, a complement-inhibitor-based treatment plan coupled with a risk evaluation and management strategy (“REMS”) and a safety support program (“SSP”) for reinforcing the REMS. The REMS and SPP are implemented using one or more computer devices with software tools programmed to enforce conditions of the REMS and/or prompt follow-ups by registered nurses enrolled in the SSP. The software tool(s) determines whether a prescriber requesting the complement inhibitor has agreed to abide by the REMS, and can prompt a provider of the complement inhibitor to provide updated educational materials to the prescriber at predetermined times or intervals, to monitor the prescriber for compliance with the REMS, and/or to monitor patients for signs of adverse events. Using exemplary embodiments described herein, a risk of adverse events (especially, but not limited to, meningococcal infections) can be managed and an incidence of the adverse events can be reduced.

Abstract: The present disclosure relates to solutions and methods of preparing lyophilized formulations of factor Xa (fXa) antidotes. A suitable aqueous formulation suitable for lyophilization can include a fXa antidote, a solubilizing agent, a stabilizer, and a crystalline component, wherein the formulation does not collapse during lyophilization.

Abstract: The disclosure provides a method of producing recombinant alkaline phosphatase comprising: (i) culturing an alkaline phosphatase in a recombinant cell culture; (ii) obtaining a preparation of recombinant alkaline phosphatase from the cell culture; and (iii) minimizing in the preparation a concentration of at least one metal ion selected from the group consisting of: Nickel (Ni), Cobalt (Co), Copper (Cu), Manganese (Mn), Chromium (Cr), and Molybdenum (Mo).

Abstract: The present disclosure provides methods for manufacturing a fXa derivative protein at large scale leading to high yield of highly pure protein product. The method may include adding a detergent to a sample that contains a polynucleotide construct encoding the protein and purifying the protein through a soybean trypsin inhibitor (STI)-based affinity chromatograph, an ion exchange and mixed mode chromatograph and a hydrophobic interaction.

Abstract: The present invention relates antidotes to anticoagulants targeting factor Xa. The antidotes are factor X and factor Xa protein derivatives that bind to the factor Xa inhibitors thereby substantially neutralizing them but do not assemble into the prothrombinase complex. The derivatives describe herein lack or have reduced intrinsic coagulant activity. Disclosed herein are methods of reversing anticoagulation, stopping or preventing bleeding in a patient that is currently undergoing anticoagulant therapy with a factor Xa inhibitor.

Abstract: The present application relates to methods and compositions employing an antibody that inhibits activation of the complement system and can be used to prevent or treat a pulmonary disease or condition.

Abstract: Provided herein are high throughput methods for measuring the protease activity of the complement C3 convertase by detecting the consumption of C3 or the production of C3a in vivo and in vitro.

Abstract: The disclosure features methods for treating hypophosphatasia (HPP) in a patient (e.g., adolescent or adult having HPP) exhibiting physical impairments or decreased walking ability by administering a soluble alkaline phosphatase (sALP) to the patient.

Abstract: Forms of cerdulatinib and salts or co-crystals thereof were prepared and characterized in the solid state. Also provided are processes of manufacture and methods of using the forms cerdulatinib and salts or co-crystals thereof.

Abstract: The present invention provides compositions of recombinant human lysosomal acid lipase having particular glycosylation patterns for internalization into target cells, a vector containing the nucleic acid encoding human lysosomal acid lipase, a host cell transformed with the vector, pharmaceutical compositions comprising the recombinant human lysosomal acid lipase and method of treating conditions associated with lysosomal acid lipase deficiency.

Abstract: Provided herein are compositions and methods for treating craniosynostosis. In particular, provided herein are methods of treating and preventing craniosynostosis by administering an isolated TNAP polypeptide or a nucleic acid molecule that encodes a TNAP polypeptide.

Abstract: Provided are methods for clinical treatment of Paroxysmal Nocturnal Hemoglobinuria (PNH) and Atypical Hemolytic Uremic Syndrome (aHUS) using an anti-C5 antibody, or antigen binding fragment thereof.

Abstract: Provided herein are methods shifting the isoelectric profile of a recombinant protein product and the use of such methods in the manufacture of recombinant protein products. Also provided are recombinant protein products produced by such methods.

Abstract: Eculizumab, a humanized monoclonal antibody against C5 that inhibits terminal complement activation, showed activity in a preliminary 12-week open-label trial in a small cohort of patients with paroxysmal nocturnal hemoglobinuria (PNH). The present study examined whether chronic eculizumab therapy could reduce intravascular hemolysis, stabilize hemoglobin levels, reduce transfusion requirements, and improve quality of life in a double-blind, randomized, placebo-controlled, multi-center global Phase III trial. It has been found that eculizumab stabilized hemoglobin levels, decreased the need for transfusions, and improved quality of life in PNH patients via reduced intravascular hemolysis. Chronic eculizumab treatment appears to be a safe and effective therapy for PNH.

Abstract: Compositions and methods relating to potentially pathogenic mutations in the nucleotide sequence of a human NAGLU gene. Some NAGLU gene variants have been discovered to be associated with reduced N-acetyl-?-D-glucosaminidase (NAGLU) activity.

Abstract: This disclosure provides methods for reducing antibody mediated rejection (AMR) in a human kidney transplant recipient, comprising administering a therapeutically effective amount of an anti-C5 antibody, or antigen-binding fragment thereof, to the recipient in a phased dosing schedule following reperfusion of a kidney allograft, wherein the recipient is sensitized to a human living donor and wherein the recipient receives about two or more weeks of desensitization therapy prior to transplantation.

Abstract: The disclosure features methods for identifying the health state of patients having hypophosphatasia (HPP). The health state of the patient, once identified, can be used to, e.g., assign a treatment regimen featuring the administration of a soluble alkaline phosphatase (sALP) to the patient, to monitor the efficacy of the treatment regimen, and/or to modify the treatment regimen. The methods also include assessing the transition of a patient with HPP from one health state to another, e.g., after completion of a treatment regimen that includes administering an sALP.

Abstract: Disclosed herein are methods for treating a subject with an alkaline phosphatase deficiency, further comprising monitoring additional anaiytes, e.g., calcium, parathyroid hormone and/or vitamin D, with treatment modifications as indicated by the levels, e.g., serum levels, of the additional anaiytes.

Abstract: Eculizumab, a humanized monoclonal antibody against C5 that inhibits terminal complement activation, showed activity in a preliminary 12-week open-label trial in a small cohort of patients with paroxysmal nocturnal hemoglobinuria (PNH). The present study examined whether chronic eculizumab therapy could reduce intravascular hemolysis, stabilize hemoglobin levels, reduce transfusion requirements, and improve quality of life in a double-blind, randomized, placebo-controlled, multi-center global Phase III trial. It has been found that eculizumab stabilized hemoglobin levels, decreased the need for transfusions, and improved quality of life in PNH patients via reduced intravascular hemolysis. Chronic eculizumab treatment appears to be a safe and effective therapy for PNH.